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Recent progress on an endogenous digitalislike factor in hypertension.

J F Cloix, M Crabos, P Meyer

    Journal of Clinical Hypertension
    |June 1, 1986
    PubMed
    Summary
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    Researchers identified a potential sodium-potassium adenosine triphosphatase (Na+, K+-ATPase) inhibitor linked to volume expansion. This compound, found in hypertensive patients

    Area of Science:

    • Cardiovascular Physiology
    • Endocrinology
    • Nephrology

    Background:

    • Extracellular volume expansion is linked to endogenous natriuretic factors.
    • Investigating plasma effects on erythrocyte [3H]ouabain binding can reveal Na+, K+-ATPase inhibitory activity.
    • Elevated ouabain-like activity has been observed in conditions like acromegaly, chronic renal failure, and hypertension.

    Purpose of the Study:

    • To investigate the presence and characteristics of a Na+, K+-ATPase inhibitor associated with volume expansion.
    • To partially purify and characterize this inhibitor from human urine.

    Main Methods:

    • Plasma from patients with extracellular volume expansion was analyzed for effects on erythrocyte [3H]ouabain binding.
    • A compound was partially purified from the urine of hypertensive patients using flash chromatography, anionic exchange, and reversed-phase HPLC.

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  • Nuclear magnetic resonance and mass spectrometry were employed for structural elucidation.

    • Main Results:

    • High levels of ouabain-like activity were detected in plasma from acromegalic, chronically renally insufficient, and some hypertensive patients.
    • A nonpeptidic compound, possibly a low molecular mass steroid (<500 daltons), was purified 400,000-fold from hypertensive patients' urine.
    • Purification involved multiple chromatographic techniques including RP 18, diphenyl, and phenyl packings.

    Conclusions:

    • A Na+, K+-ATPase inhibitor, potentially a steroid, is associated with volume expansion and hypertension.
    • This inhibitor can be partially purified from the urine of hypertensive individuals.
    • Further characterization is needed to confirm the structure and precise role of this compound in cardiovascular regulation.